摘要：Runt-related transcription factor 2
(Runx2)-deficient mice can be used to model congenital tooth agenesis in humans. Conversely, uterine sensitization-associated gene-1 (
Usag-1)-deficient mice exhibit supernumerary tooth formation. Arrested tooth formation can be restored by crossing both knockout-mouse strains; however, it remains unclear whether topical inhibition of
Usag-1 expression can enable the recovery of tooth formation in
Runx2-deficient mice. Here, we tested whether inhibiting the topical expression of
Usag-1 can reverse arrested tooth formation after
Runx2 abrogation. The results showed that local application of
Usag-1 Stealth small interfering RNA (siRNA) promoted tooth development following
Runx2 siRNA-induced agenesis. Additionally, renal capsule transplantation of siRNA-loaded cationized, gelatin-treated mouse mandibles confirmed that cationized gelatin can serve as an effective drug-delivery system. We then performed renal capsule transplantation of wild-type and
Runx2-knockout (KO) mouse mandibles, treated with
Usag-1 siRNA, revealing that hindered tooth formation was rescued by
Usag-1 knockdown. Furthermore, topically applied
Usag-1 siRNA partially rescued arrested tooth development in
Runx2-KO mice, demonstrating its potential for regenerating teeth in
Runx2-deficient mice. Our findings have implications for developing topical treatments for congenital tooth agenesis.
